Author | Queto, Tulio | |
Author | Xavier-Elsas, Pedro Paulo | |
Author | Gardel, Marcelo Aranha | |
Author | Luca, Bianca de | |
Author | Barradas, Mônica | |
Author | Masid, Daniela | |
Author | Silva, Patricia Machado R. e | |
Author | Peixoto, Christina A. | |
Author | Vasconcelos, Zilton Farias Meira de | |
Author | Dias, Eliane P. | |
Author | Gaspar-Elsas, Maria Ignez | |
Access date | 2015-02-26T14:42:14Z | |
Available date | 2015-02-26T14:42:14Z | |
Document date | 2010 | |
Citation | QUETO, Tulio et al. Inducible nitric oxide synthase/CD95L-dependent suppression of pulmonary and bone marrow eosinophilia by diethylcarbamazine. American Journal of Respiratory and Critical Care Medicine, New York, v. 181, p. 429-437, 2010. | pt_BR |
ISSN | 1073-449X | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/9547 | |
Language | eng | pt_BR |
Publisher | American Thoracic Society | pt_BR |
Rights | restricted access | |
Title | Inducible nitric oxide synthase/CD95L-dependent suppression of pulmonary and bone marrow eosinophilia by diethylcarbamazine | pt_BR |
Type | Article | pt_BR |
DOI | 10.1164/rccm.200905-0800OC | |
Abstract | Rationale: The mechanism of action of diethylcarbamazine (DEC), an
antifilarial drug effective against tropical pulmonary eosinophilia,
remains controversial. DEC effects on microfilariae depend on in-ducible NO synthase (iNOS). In eosinophilic pulmonary inflam-mation, its therapeutic mechanism has not been established. We
previously described the rapid up-regulation of bone marrow
eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway
allergen challenge, and further evidenced the down-regulation of
eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms.
Objectives: We investigated whether: (1) DEC can prevent the effects
of airway challenge of sensitized mice on lungs and bone marrow,
and (2) its effectiveness depends on iNOS/CD95L.
Methods: OVA-sensitized BALB/c mice were intranasally challenged
for 3 consecutive days, with DEC administered over a 12-, 3-, or 2-day
period, ending at the day of the last challenge. We evaluated: (1)
airway resistance, cytokine (IFN-g, IL-4, IL-5, and eotaxin) produc-tion, and pulmonary eosinophil accumulation; and (2) bone marrow
eosinophil numbersin vivoand eosinophil differentiationex vivo.
Measurements and Main Results: DEC effectively prevented the effects
of subsequent challenges on: (1) airway resistance, Th1/Th2 cyto-kine production, and pulmonary eosinophil accumulation; and (2)
eosinophilopoiesisin vivo andex vivo. Recovery from unprotected
challenges included full responses to DEC during renewed chal-lenges. DEC directly suppressed IL-5–dependent eosinophilopoiesis
in naive bone marrow. DEC was ineffective in CD95L-deficient gld
mice and in mice lacking iNOS activity because of gene targeting or
pharmacological blockade.
Conclusions: DEC has a strong impact on pulmonary eosinophilic
inflammation in allergic mice, as well as on the underlying hemo-poietic response, suppressing the eosinophil lineage by an iNOS/
CD95L-dependent mechanism. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Rio de Janeiro, RJ, Brasil. / Centro de Tecnologias Estratégicas do Nordeste. Laboratório de Microscopia e Microanálise. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Faculdade de Medicina. Programa de Pós-graduação em Patologia. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Fisiopatologia Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Eosinophils | pt_BR |
Subject | Diethylcarbamazine | pt_BR |
Subject | Bone Marrow | pt_BR |
Subject | Inducible NO Synthase | pt_BR |
Subject | CD95L | pt_BR |
DeCS | Eosinófilos | pt_BR |
DeCS | Dietilcarbamazina | pt_BR |
DeCS | Medula Óssea | pt_BR |
DeCS | Ligases | pt_BR |